DOCSLIB.ORG

Salmonella Through Cross- Presentation 7

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Salmonella Through Cross- Presentation 7 UvA-DARE (Digital Academic Repository) B and T cell crosstalk in anti-bacterial immune responses de Wit, J. Publication date 2012 Link to publication Citation for published version (APA): de Wit, J. (2012). B and T cell crosstalk in anti-bacterial immune responses. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:27 Sep 2021 Antigen-specific B cells reactivate an effective cytotoxic T cell response against phagocytosed Salmonella through cross- presentation 7 Jelle de Wit, Yuri Souwer, Tineke Jorritsma, Hanny Klaasse Bos, Anja ten Brinke, Jacques Neefjes and S. Marieke van Ham PLoS One. 2010 Sep 27;5(9):e13016 Chapter 7 Abstract The eradication of facultative intracellular bacterial pathogens, like Salmonella typhi, requires the concerted action of both the humoral immune response and the cytotoxic CD8+ T cell response. Dendritic cells (DCs) are considered to orchestrate the cytotoxic CD8+ T cell response via cross-presentation of bacterial antigens onto MHC class I molecules. Cross-presentation of Salmonella by DCs however, is accompanied by the induction of apoptosis in the DCs. Besides antibody production, B cells are required to clear Salmonella infection for other unknown reasons. Here we show that Salmonella- specific B cells that phagocytoseSalmonella upon BCR-ligation reactivate human memory CD8+ T cells via cross-presentation yielding aSalmonella -specific cytotoxic T cell response. The reactivation of CD8+ T cells is dependent on CD4+ T cell help. Unlike the DCs, B cell- mediated cross-presentation ofSalmonella does not coincide with apoptosis. B cells form a new player in the activation of the cytotoxic effector arm of the immune response and the generation of effective adaptive immunity inSalmonella infection. 142 Cross-presentation by B cells Introduction Salmonella is a pathogenic bacterium that causes severe disease in mice and man. Salmonella typhi (Salmonella enterica serovar Typhi) causes invasive diseases in human, which has many features in common with Salmonella typhimurium in mice. The gastrointestinal tract is the major site of primary infection of the host and has to be passed before systemic infection can occur. One way to infect the host cells is via sampling of bacteria by DCs in the intestine. In vitro studies showed that DCs located in the lamina propria under the gut epithelium of the small bowel extend processes across the tight junctions between the epithelial cells and capture bacteria from the luminal side of the gut.1, 2 The major route of infection however, is via microfold cells or M cells.3, 4 The specialized antigen-sampling M cells are located in the dome region of the Peyer’s Patches and are efficient in transportation of macromolecules and microorganisms to the underlying immune cells.2, 5 Like other Gram-negative bacteria, Salmonella uses specific virulence factors to invade other cell types, called the Type III Secretion System (TTSS). Many Salmonella virulence genes are clustered in Salmonella pathogenicity islands (SPIs). SPI-1 and SPI-2 encode TTSSs that mediate the injection of effector proteins into the host cell cytoplasm via sophisticated secretion devices.6 SPI-1 is associated with invasion of intestinal epithelia and enhanced intestinal inflammation in the infected host.7, 8 SPI-2 modulates intracellular trafficking and enables replication within a modified vacuolar compartment, called the Salmonella-containing vacuole (SCV) 9-11 and enhances inflammation during enteric phase.12, 13 Salmonella activates the PKB/Akt1 pathway to prevent maturation of SCV into destructive phagolysosomes, thus manipulating the host for its own survival.14 After transcytosis by M cells, Salmonella reaches the subepithelial dome of the Peyer’s patches and encounters an extensive network of resident macrophages, DCs and great C h a p t e r 7 numbers of B cells.15, 16 Instead of being immediately destroyed by these cells, Salmonella have evolved several mechanisms to survive in the harsh milieu of phagosomal compartments 17 and can be cytotoxic to macrophages by inducing apoptosis in vitro.18, 19 Recently, we showed that recognition ofSalmonella via the specific B cell receptor (BCR) on B cells results in internalization ofSalmonella . Salmonella is able to survive intracellularly in primary B cells in a non-replicative state.20 Following uptake of Salmonella, B cells do not go into apoptosis, but differentiate and start to produce Salmonella-specific antibodies. In addition, BCR-mediated phagocytosis of Salmonella by B cells leads to antigen presentation via MHC class II and subsequent CD4+ T cell activation, which in turn boosts antibody production by the infected B cell. Antibody transfer studies have shown that the requirement for B cells in the clearance of 143 Chapter 7 Salmonella does not solely depend on antibody formation.21 Which additional immune responses need B cell involvement remains unclear. For clearance of Salmonella, not only the humoral immune response is required, but also the activation of cytotoxic CD8+ T cells is needed to eliminate Salmonella-infected cells. Recently, DCs have been shown to activate Salmonella-specific CD8+ memory T cells after direct uptake of bacteria or via suicide cross-presentation after uptake of S. typhi-infected human cells.22 As the generation of Salmonella antigens for MHC class II molecules is an efficient process in infected B cells, we tested whether BCR-mediated phagocytosis also leads to cross- presentation of Salmonella antigens via the MHC class I pathway of B cells and whether this elicits a cytotoxic T cell response against Salmonella-infected cells. Here we show that Salmonella-specific primary B cells that have internalized Salmonella do cross-present Salmonella antigens via MHC class I in a proteasome-dependent manner. Cross-presentation ofSalmonella antigens by B cells reactivatesSalmonella -specific CD8+ memory cells that acquire a cytotoxic phenotype and are efficient in killing ofSalmonella - infected cells. Thus, antigen-specific B cells are an under appreciated type of cell for the induction of a cytotoxic T cell response against facultative intracellular bacteria. Materials and methods Antibodies and fluorophores mAb anti-human IgM (MH15, Sanquin, Amsterdam, The Netherlands) was mixed with rat anti-mouse IgG1 antibody (RM161.1, Sanquin) and mAb anti-S. typhimurium LPS (1E6, Biodesign International, Kennebunk, ME) to generate BCR-LPS tetrameric antibody complexes, used to coat bacteria as previously described.20 Antagonist anti-human CD40 mouse monoclonal antibody was a kind gift of Dr. L. Boon. The following labeled anti-human mAbs were obtained from BD Biosciences (San Jose, CA): anti-IFN-γ-FITC, anti-CD27-PE, anti-CD107a-PE, anti-CD8-PerCP-Cy5.5, anti-CD4-APC, anti-CD45RO-PE, AnnexinV-APC and IgG1-PerCP-Cy5.5 isotype control. FITC-conjugated antibody IgG1, IgG2a and IgG2b, IgG1-PE and IgG1-APC isotype controls and PE- conjugated anti-CD8 blocking antibody were obtained from DAKO (Glostrup, Denmark). Anti-CD45RA-FITC and anti-CD45RO-FITC were obtained from Sanquin and DAPI from Sigma-Aldrich (Steinheim, Germany). CFSE (Invitrogen, Paisley, UK) labeling was used in proliferation assays. Bacterial growth conditions GFP expressing-S. typhimurium SL1344 was described before.33 GFP-Salmonella defective 144 Cross-presentation by B cells in SPI-1 (invA mutant) or SPI-2 (ssrA mutant) were a kind gift of M. Rescigno (European Institute of Oncology, Milan, Italy). Staphylococcus aureus expressing GFP (RN4220 with pWVW189GFP) was kindly provided by S. A. J. Zaat (Academic Medical Center, Amsterdam, The Netherlands). All bacteria strains were grown overnight at 37ºC in Luria- Bertani (LB) broth with carbenicillin or chloramphenicol (Sigma-Aldrich, St Louis, MO) to maintain GFP expression while shaking, subcultured at a dilution of 1:33 in fresh LB medium and incubated while shaking at 37ºC for 3 to 4 hours to obtain exponentially growing bacteria. For coating, bacteria were washed twice with PBS and incubated with BCR-LPS tetrameric antibody complexes for 30 minutes at room temperature and washed twice with PBS to remove unbound antibodies. For experiments with dead Salmonella, bacteria were heat killed by incubation at 65°C for 15 minutes. Lymphocyte isolation and B lymphocyte infection with Salmonella Human PBMCs were isolated by centrifugation on a Ficoll-Hypaque gradient (Axis- Shield PoC AS, Oslo, Norway) from a buffycoat obtained from healthy donors (Sanquin). All donors provided written informed consent in accordance with the protocol of the local institutional review board, the Medical Ethics Committee of Sanquin Bloodbank (Amsterdam, The Netherlands), and the Medical Ethics Committee of Sanquin approved the study. B and T cells were subsequently purified using anti-CD19, anti-CD4, anti-CD8 Dynabeads and DETACHaBEAD (Invitrogen), according to the manufacturer’s instructions. Monocytes were isolated by positive selection using CD14 microbeads and a magnetic cell separator (MACS, Miltenyi Biotec, Bergisch Gladbach, Germany). Monocytes were cultured at a concentration of 1×106 cells/ml in 20 ml Cellgro medium (CellGenix, Freiburg, Germany) supplemented with GM-CSF (1,000 IU/ml; Cellgenix) and IL-4 (800 IU/ml; Cellgenix) in a 80 cm2 cell culture flask (Nunc, Roskilde Denmark) to generate immature DCs.
Load more

Recommended publications
  • Thesis Indesign Option 2.Indd
    Cover Page The following handle holds various files of this Leiden University dissertation: http://hdl.handle.net/1887/67915 Author: Schunselaar, L.M. Title: The search for new treatment strategies for malignant pleural mesothelioma Issue Date: 2019-01-15 Addendum - Curriculum Vitae Curriculum Vitae Laurel Schunselaar was born on the 17th of August, 1987, in Enschede. After receiving her VWO diploma at the Bonhoeffer College van der Waalslaan in Enschede, she started her study Technical Medicine at the University of Twente in 2005. After obtaining her bachelor degree in 2008, she continued with her masters. During this master she followed four clinical research internships in which both research and clinical activities were the focus. She started at the Dutch Burn Centre in Beverwijk, after which she moved to Utrecht for the second and third internship at the department of trauma surgery and the department of orthopedics in the University Medical Center. During her internship at the Antoni van Leeuwenhoek in Amsterdam she became acquainted with screening chemotherapy on mesothelioma cells. For her master thesis project she stayed at the Antoni van Leeuwenhoek – Netherlands Cancer Institute and worked for one year on the development of short term primary tumor cultures of mesothelioma cells for screening and development of new therapeutic compounds. At the end of 2012 she obtained her master degree in Technical Medicine and started as a PhD student in the Antoni van Leeuwenhoek - Netherlands Cancer Institute. In the group of Prof. Dr Jacques Neefjes and later Prof. Dr. Zwart, but always in close collaboration with the thoracic oncology group of Prof.
    [Show full text]
  • Following Is a List of Lecturers Who Have Participated in Mcgill's Beatty
    Following is a list of lecturers who have participated in McGill’s Beatty Talks as well as their affiliated organization, titles of their presentations, date of the event, and sponsoring group or groups. 2010s Margaret Rossiter "Women in Science and Medicine: Reflections on a Century" October 13, 2012 Science Outreach, Redpath Museum, McGill Institute for the Study of Canada, History and Classical Studies, Medicine Catherine Driscoll University of Sydney, Australia "Media, Social Change and Lives of Girls" October 11, 2012 Arts, Institute of Gender, Sexuality, and Feminist Studies Jeremy Waldron All Souls College, University of Oxford "The Rule of Law and the Measure of Property" October 4, 2012 Arts Francis Fukuyama Stanford University "The Origins of Political Order" September 23, 2012 Political Science Andrew Chanen University of Melbourne "Borderline Personality Disorder in Adolescents" May 10, 2012 Royal Victoria Hospital, Psychiatry Michael Kearney Palliative Care Service Santa Barbara Cottage Hospital "Lessons in Living from the Dying: Whole Person Self-Care" May 8, 2012 Council on Palliative Care Jacques Neefjes Netherlands Cancer Institute "A Genome-Wide Multidimentional RNAi Screen Reveals Pathways Controlling MHC Class II Antigen Presentation" February 27, 2012 Microbiology and Immunology Harvey V. Fineberg Institute of Medicine "The Health Populations: Roles and Responsibilities for the 21st Century" February 16-17, 2012 Epidemiology, Biostatistics and Occupational Health Michael Holquist Yale University "Why the Humanities
    [Show full text]
  • For Every Professional in the Immunology Chain
    Volume 4 - Issue 3 - December 2015 - IMMUUNfor every professional in the immunology chain Exercise immunology NVVI Winter School 2015 A world to discover December 16 & 17 Noordwijkerhout Longfonds: “Focus on end result” Paul Parren: Mining for novel drugs theme exerciSe aNd LuNgS Sjaak Neefjes VaN Loghem Laureate Youth? it’s in the blood! Contains NVVI Winter School Programme, p 30 Have CONFIDENCE in your multiplex immunoassays. Our rigorous validation process delivers performance and quality. When processing samples for a clinical study or for the development of a new drug therapy, it’s critical to generate reproducible data. As a leading supplier of Luminex based assays, Affymetrix ensures that each ProcartaPlex® Immunoassay passes more than 30 qualification criteria to ensure optimum lot-to-lot reproducibility, accuracy, and sensitivity. We built confidence into the performance and quality of our assays, so you can have total confidence in your research. We deliver confidence AND provide flexibility: n Off the shelf, biologically relevant panels n Custom panels for total flexibility n Over 350 combinable assays for 6 species See how we build confidence into our assays: www.affymetrix.com/ProcartaPlex © 2015 Affymetrix, Inc. All rights reserved. For Research Use Only. Not for use in diagnostic procedures. LMNX06206-Ad-Print-PPX_Confidence_Campaign-DDN-Nov_1015.indd 1 10/7/15 4:15 PM COLOPHON contents IMMUUN December 2015 Immuun is published by the NVVI and written and edited by Bureau Lorient Communicatie BV. In 2015, Immuun will have three issues. The target Column groups are NVVI members, relevant clinicians, suppliers and other 4News 5Q&A partners of immunologists as well as policy makers.
    [Show full text]
  • Interference with T Cell Receptor–HLA-DR Interactions by Epstein–Barr Virus Gp42 Results in Reduced T Helper Cell Recognition
    Interference with T cell receptor–HLA-DR interactions by Epstein–Barr virus gp42 results in reduced T helper cell recognition Maaike E. Ressing†, Daphne van Leeuwen†, Frank A. W. Verreck‡, Raquel Gomez§, Bianca Heemskerk¶, Mireille Toebes§, Maureen M. Mullenʈ, Theodore S. Jardetzkyʈ, Richard Longnecker††, Marco W. Schilham¶, Tom H. M. Ottenhoff‡, Jacques Neefjes‡‡, Ton N. Schumacher§, Lindsey M. Hutt-Fletcher§§, and Emmanuel J. H. J. Wiertz†¶¶ Departments of †Medical Microbiology, ‡Immunohematology and Blood Transfusion, and ¶Pediatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Divisions of §Immunology and ‡‡Tumor Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; Departments of ʈBiochemistry and ††Microbiology, Northwestern University, Evanston, IL 60208; and §§Departments of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, LA 71104 Communicated by Johannes van Rood, Europdonor Foundation, Leiden, The Netherlands, August 5, 2003 (received for review May 22, 2003) Epstein–Barr virus (EBV) persists lifelong in infected hosts despite with the notable exception of Epstein–Barr nuclear antigen 1 the presence of antiviral immunity. Many viral antigens are ex- (EBNA1), the only protein required for persistence of the viral pressed during lytic infection. Thus, for EBV to spread, it must have episome. EBNA1 escapes from MHC class I-restricted presen- evolved effective ways to evade immune recognition. Here, we tation to CTL by blocking its proteasomal degradation and, report that HLA class II-restricted antigen presentation to T helper thereby, the generation of antigenic peptides (reviewed in refs. cells is hampered in the presence of the lytic-phase protein gp42. 5 and 6). In contrast, during lytic infection, Ϸ100 EBV proteins This interference with T cell activation involves association of gp42 are synthesized for the production of infectious virus, which with class II peptide complexes.
    [Show full text]
  • Loading Proteasome Activity and MHC Class I Peptide Allelic Differences in the Relationship Between
    Allelic Differences in the Relationship Between Proteasome Activity and MHC Class I Peptide Loading This information is current as Adam M. Benham, Monique Grommé and Jacques Neefjes of September 24, 2021. J Immunol 1998; 161:83-89; ; http://www.jimmunol.org/content/161/1/83 Downloaded from References This article cites 48 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/161/1/83.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 24, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Allelic Differences in the Relationship Between Proteasome Activity and MHC Class I Peptide Loading1 Adam M. Benham, Monique Gromme´, and Jacques Neefjes2 MHC class I molecules are cell surface glycoproteins that play a pivotal role in the response to intracellular pathogens. The loading of MHC class I molecules with antigenic substrates takes place in the endoplasmic reticulum.
    [Show full text]
  • Bacterial Infections and Cancer
    Review Bacterial infections and cancer Daphne van Elsland & Jacques Neefjes* Abstract cancerous state of uncontrolled cell division. It is now understood how viruses such as hepatitis B virus and human papillomavirus Infections are estimated to contribute to 20% of all human types 5 and 8 cause cellular transformation by inducing genetic tumours. These are mainly caused by viruses, which explains why a instability through viral integration and through the activation of a direct bacterial contribution to cancer formation has been largely large number of signalling pathways and cellular genes involved in ignored. While epidemiological data link bacterial infections to oncogenesis, proliferation, inflammation and immune responses particular cancers, tumour formation is generally assumed to be [9,10]. solely caused by the ensuing inflammation responses. Yet, many Viruses do, however, represent only one segment of the micro- bacteria directly manipulate their host cell in various phases of biome that exploits the mammalian host during its infection cycle. their infection cycle. Such manipulations can affect host cell integ- Pathogenic moulds, helminths and bacteria intensively interact with rity and can contribute to cancer formation. We here describe how mammalian host cells to ensure their survival. Although these bacterial surface moieties, bacterial protein toxins and bacterial microorganisms usually do not leave a genetically recognizable trait effector proteins can induce host cell DNA damage, and thereby or piggyback on mammalian genes, such as illustrated by viral can interfere with essential host cell signalling pathways involved infections, strong epidemiological links exist between various micro- in cell proliferation, apoptosis, differentiation and immune biological infections and cancers (Table 1).
    [Show full text]
  • List of Publications Curriculum Vitae Acknowledgements
    Cover Page The handle http://hdl.handle.net/1887/85320 holds various files of this Leiden University dissertation. Author: Luimstra, J.J. Title: Immunochemical approaches to monitor and modulate the adaptive immune system Issue Date: 2020-02-12 List of publications List of publications Luimstra, J.J.; Neefjes, J.; Borst, J.G.; Ovaa, H. The future of cancer immunotherapy: opportunities for small molecules. Manuscript under revision Luimstra, J.J.; Franken, C.L.M.C.; Garstka, M.A.; Drijfhout, J.W.; Neefjes, J.; Ovaa, H. Production and thermal exchange of conditional peptide-MHC I multimers. Current Protocols in Immunology 126, e85 (2019) Luimstra, J.J.*; Garstka, M.A.*; Roex, M.C.J.; Redeker, A.; Janssen, G.M.C.; Van Veelen, P.A.; Arens, R.; Falkenburg, J.H.F.; Neefjes, J.; Ovaa, H. A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells. Journal of Experimental Medicine 215, 1493-1504 (2018) Rosendahl Huber, S.K.*; Luimstra, J.J.*; Van Beek, J.; Hoppes, R.; Jacobi, R.H.; Hendriks, M.; Kapteijn, K.; Ouwerkerk, C.; Rodenko, B.; Ovaa, H.; De Jonge, J. Chemical modification of influenza CD8+ T-cell epitopes enhances their immunogenicity regardless of immunodominance. PLoS One 11, e0156462 (2016) Hoppes, R.*; Oostvogels, R.*; Luimstra, J.J.; Wals, K.; Toebes, M.; Bies, L.; Ekkebus, R.; Rijal, P.; Celie, P.H.; Huang, J.H.; Emmelot, M.E.; Spaapen, R.M.; Lokhorst, H.; Schumacher, T.N.; Mutis, T.; Rodenko, B.; Ovaa, H. Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes. Journal of Immunology 193, 4803-4813 (2014) *These authors contributed equally.
    [Show full text]
  • Typhoid Bacteria Linked to Gallbladder Cancer
    Typhoid Bacteria Linked To Gallbladder Cancer - June 08, 2015 Asian Scientist Magazine | Science, Technology and Medicine News Updates From Asia - http://www.asianscientist.com Typhoid Bacteria Linked To Gallbladder Cancer June 08, 2015 http://www.asianscientist.com/2015/06/health/typhoid-bacteria-linked-gallbladder-cancer/ AsianScientist (Jun. 8, 2015) - Controlling bacterial infections responsible for typhoid fever could dramatically reduce the risk of gallbladder cancer in India and Pakistan, according to a study published in Cell Host & Microbe. The findings establish for the first time the causal link between bacterial infection and gallbladder cancer, explaining why this type of cancer is rare in the West but common in India and Pakistan, where typhoid fever is endemic. Public policy changes inspired by this research could have an immediate impact on preventing a type of cancer that currently has a very poor prognosis. “While viruses are among the established causal factors for particular cancers, bacteria are largely ignored as direct contributors,” says senior study author Professor Jacques Neefjes of the Netherlands Cancer Institute. “Accepting that bacterial infections can directly contribute to cancer formation makes these tumors in principle preventable. If Salmonella Typhi infections are cured immediately with antibiotics and chronic infections are prevented, or if vaccination programs to eradicate S. Typhi work, we would expect a major reduction in the incidence of a tumor that represents the third most common gastrointestinal tumor in India and Pakistan.” Gallbladder cancer is hard to diagnose in its early stages because there are no signs or symptoms. By the time the cancer is detected, it is often too late to save patients' lives.
    [Show full text]
  • Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: a Narrative Review
    UvA-DARE (Digital Academic Repository) Feasibility of primary tumor culture models and preclinical prediction assays for head and neck cancer: A narrative review Dohmen, A.J.C.; Swartz, J.E.; Van Den Brekel, M.W.M.; Willems, S.M.; Spijker, R.; Neefjes, J.; Zuur, C.L. DOI 10.3390/cancers7030858 Publication date 2015 Document Version Final published version Published in Cancers License CC BY Link to publication Citation for published version (APA): Dohmen, A. J. C., Swartz, J. E., Van Den Brekel, M. W. M., Willems, S. M., Spijker, R., Neefjes, J., & Zuur, C. L. (2015). Feasibility of primary tumor culture models and preclinical prediction assays for head and neck cancer: A narrative review. Cancers, 7(3), 1716-1742. https://doi.org/10.3390/cancers7030858 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:01 Oct 2021 Cancers 2015, 7, 1716-1742; doi:10.3390/cancers7030858 cancersOPEN ACCESS ISSN 2072-6694 www.mdpi.com/journal/cancers Review Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review Amy J.
    [Show full text]
  • LST Projects @ LUMC
    Research projects @LUMC for MSc LST Example projects from recent years Human Genetics Cell & Chemical Biology Research at the department of Human Genetics is clustered in four The division of Cell & Chemical Biology aims to unravel the research programmes: molecular details of the working of cells in their normal function • Functional Genomics of Muscle, Nerve and Brain Disorders and the perturbed functioning in diseased cells and to help • Genome Instability and Cancer translate our knowledge and technologies to clinical practice. • Molecular Technology and Informatics for Personalised Medicine Infection and transformation efficiency of Salmonella isolates and Health from patients who developed colon cancer • Functional Genomics of Systemic Disorders group of Jacques Neefjes (Chemical immunology) Identification of hELOF1 and its role in Transcription-coupled Figure: Infection efficiency of sixty Nucleotide Excision Repair Salmonella isolates in MEFs Arf- /- + c- MYC at MOI 20. Red bars indicate isolates group of Martijn Luijsterburg (Regulation and Dynamics of Nucleotide associated with cancer and green bars indicate Excision Repair) isolates non-associated with colon cancer. YAP and TAZ: growing drug targets for uveal melanoma group of Aart Jochemsen (Molecular cell biology) Figure: Growth inhibition of OMM2.5 cells after 5-day treatment with doxy or not. Growth inhibition is largest in case of a TAZ knockdown, but also observable in YAP knockdowns. Figure: Loss of hELOF1 results in illudin S sensitivity. Schematic representation of the illudin S genome-wide CRISPR-Cas9 screen. RPE-I cells are transduced with a lentiviral library targeting 18,056 human protein-coding genes and positive cells are selected with puromycin. Illudin S sensitizes cells when they are KO for transcription-coupled nucleotide excision repair (TCR).
    [Show full text]
  • Systems Microbiology Current Topics and Applications
    Systems Microbiology Current Topics and Applications Edited by Brian D. Robertson Centre for Integrated Systems Biology and Bioinformatics Imperial College London and Brendan W. Wren London School of Hygiene and Tropical Medicine London UK Caister Academic Press Copyright © 2012 Caister Academic Press Norfolk, UK www.caister.com British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-1-908230-02-7 Description or mention of instrumentation, software, or other products in this book does not imply endorsement by the author or publisher. The author and publisher do not assume responsibility for the validity of any products or procedures mentioned or described in this book or for the consequences of their use. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher. No claim to original U.S. Government works. Cover design adapted from Figures 3.2 and 6.3. Printed and bound in Great Britain Contents Contributors v Preface ix 1 Mathematical Models for Systems Biology and How to Construct Them 1 Chris P. Barnes, Maxime Huvet, Nathan Harmston and Michael P.H. Stumpf 2 Dynamics and Robustness of Metabolic Networks: A Systems Biology Review of Escherichia coli Metabolism 17 Eivind Almaas, Per Bruheim, Rahmi Lale and Svein Valla 3 Bacterial Chemotaxis: Rising Complexity 47 Diana Clausznitzer, Judith P. Armitage and Robert G. Endres 4 Systems Biology of Infection: The Pathogen Perspective 69 Dirk Bumann 5 Manipulating the Fight Between Human Host Cells and Intracellular Pathogens 77 Rico Barsacchi, Varadharajan Sundaramurthy, Kees Korbee, Jacques Neefjes, Tom H.M.
    [Show full text]
  • Ultrastructural Imaging of Salmonella–Host Interactions Using Super‐Resolution Correlative Light‐Electron Microscopy of Bi
    Ultrastructural imaging of Salmonella-Host interactions using super-resolution correlative light-electron microscopy of bioorthogonal pathogens Citation for published version (APA): van Elsland, D. M., Pujals, S., Bakkum, T., Bos, E., Oikonomeas-Koppasis, N., Berlin, I., Neefjes, J., Meijer, A. H., Koster, A. J., Albertazzi, L., & van Kasteren, S. I. (2018). Ultrastructural imaging of Salmonella-Host interactions using super-resolution correlative light-electron microscopy of bioorthogonal pathogens. ChemBioChem, 19(16), 1766-1770. https://doi.org/10.1002/cbic.201800230 DOI: 10.1002/cbic.201800230 Document status and date: Published: 16/08/2018 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.
    [Show full text]